Skip to main content
Top
Published in: Brain Structure and Function 1/2019

01-01-2019 | Original Article

A suprachiasmatic-independent circadian clock(s) in the habenula is affected by Per gene mutations and housing light conditions in mice

Authors: Nora L. Salaberry, Hélène Hamm, Marie-Paule Felder-Schmittbuhl, Jorge Mendoza

Published in: Brain Structure and Function | Issue 1/2019

Login to get access

Abstract

For many years, the suprachiasmatic nucleus (SCN) was considered as the unique circadian pacemaker in the mammalian brain. Currently, it is known that other brain areas are able to oscillate in a circadian manner. However, many of them are dependent on, or synchronized by, the SCN. The Habenula (Hb), localized in the epithalamus, is a key nucleus for the regulation of monoamine activity (dopamine, serotonin) and presents circadian features; nonetheless, the clock properties of the Hb are not fully described. Here, we report, first, circadian expression of clock genes in the lateral habenula (LHb) under constant darkness (DD) condition in wild-type mice which is disturbed in double Per1−/−-Per2Brdm1 clock-mutant mice. Second, using Per2::luciferase transgenic mice, we observed a self-sustained oscillatory ability (PER2::LUCIFERASE bioluminescence rhythmicity) in the rostral and caudal part of the Hb of arrhythmic SCN-ablated animals. Finally, in Per2::luciferase mice exposed to different lighting conditions (light-dark, constant darkness or constant light), the period or amplitude of PER2 oscillations, in both the rostral and caudal Hb, were similar. However, under DD condition or from SCN-lesioned mice, these two Hb regions were out of phase, suggesting an uncoupling of two putative Hb oscillators. Altogether, these results suggest that an autonomous clock in the rostral and caudal part of the Hb requires integrity of circadian genes to tick, and light information or SCN innervation to keep synchrony. The relevance of the Hb timing might reside in the regulation of circadian functions linked to motivational (reward) and emotional (mood) processes.
Appendix
Available only for authorised users
Literature
go back to reference Bae K, Jin X, Maywood ES et al (2001) Differential functions of mPer1, mPer2, and mPer3 in the SCN circadian clock. Neuron 30:525–536CrossRefPubMed Bae K, Jin X, Maywood ES et al (2001) Differential functions of mPer1, mPer2, and mPer3 in the SCN circadian clock. Neuron 30:525–536CrossRefPubMed
go back to reference Christoph GR, Leonzio RJ, Wilcox KS (1986) Stimulation of the lateral habenula inhibits dopamine-containing neurons in the substantia nigra and ventral tegmental area of the rat. J Neurosci 6:613–619CrossRefPubMed Christoph GR, Leonzio RJ, Wilcox KS (1986) Stimulation of the lateral habenula inhibits dopamine-containing neurons in the substantia nigra and ventral tegmental area of the rat. J Neurosci 6:613–619CrossRefPubMed
go back to reference Paxinos G, Franklin KBJ (2001) The mouse brain in stereotaxic coordinates, 2 edn. Academic Press, San Diego Paxinos G, Franklin KBJ (2001) The mouse brain in stereotaxic coordinates, 2 edn. Academic Press, San Diego
go back to reference Pittendrigh CS, Daan SA (1976) Functional analysis of circadian pacemakers in nocturnal rodents. V. Pacemaker structure: a clockfor all seasons. J Comp Physiol A 106:333–355CrossRef Pittendrigh CS, Daan SA (1976) Functional analysis of circadian pacemakers in nocturnal rodents. V. Pacemaker structure: a clockfor all seasons. J Comp Physiol A 106:333–355CrossRef
go back to reference Preitner N, Damiola F, Lopez-Molina L et al (2002) The orphan nuclear receptor REV-ERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator. Cell 110:251–260CrossRefPubMed Preitner N, Damiola F, Lopez-Molina L et al (2002) The orphan nuclear receptor REV-ERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator. Cell 110:251–260CrossRefPubMed
go back to reference Shieh K-R (2003) Distribution of the rhythm-related genes rPERIOD1, rPERIOD2, and rCLOCK, in the rat brain. Neuroscience 118:831–843CrossRefPubMed Shieh K-R (2003) Distribution of the rhythm-related genes rPERIOD1, rPERIOD2, and rCLOCK, in the rat brain. Neuroscience 118:831–843CrossRefPubMed
go back to reference Sutherland RJ (1982) The dorsal diencephalic conduction system: a review of the anatomy and functions of the habenular complex. Neurosci Biobehav Rev 6:1–13CrossRefPubMed Sutherland RJ (1982) The dorsal diencephalic conduction system: a review of the anatomy and functions of the habenular complex. Neurosci Biobehav Rev 6:1–13CrossRefPubMed
go back to reference Xu H, Zhang C, Zhao H (2015) Effect of suprachiasmatic nucleus lesion on Period2 and C-fos expression in habenular nucleus. Int J Chem 7:163CrossRef Xu H, Zhang C, Zhao H (2015) Effect of suprachiasmatic nucleus lesion on Period2 and C-fos expression in habenular nucleus. Int J Chem 7:163CrossRef
go back to reference Zheng B, Albrecht U, Kaasik K et al (2001) Nonredundant roles of the mPer1 and mPer2 genes in the mammalian circadian clock. Cell 105:683–694CrossRefPubMed Zheng B, Albrecht U, Kaasik K et al (2001) Nonredundant roles of the mPer1 and mPer2 genes in the mammalian circadian clock. Cell 105:683–694CrossRefPubMed
Metadata
Title
A suprachiasmatic-independent circadian clock(s) in the habenula is affected by Per gene mutations and housing light conditions in mice
Authors
Nora L. Salaberry
Hélène Hamm
Marie-Paule Felder-Schmittbuhl
Jorge Mendoza
Publication date
01-01-2019
Publisher
Springer Berlin Heidelberg
Published in
Brain Structure and Function / Issue 1/2019
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI
https://doi.org/10.1007/s00429-018-1756-4

Other articles of this Issue 1/2019

Brain Structure and Function 1/2019 Go to the issue